GPRC5A regulates keratinocyte adhesion and migration through nuclear translocation of its C-terminus region
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PROVIDER: PRJNA1043579 | ENA |
REPOSITORIES: ENA
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Project description:G-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) is well-documented in lung and various epithelial cancers. However, its role in the skin remains unexplored. In this study, we investigated the function of this receptor in skin biology and our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed GPRC5A reinduction during wound healing at the leading edges in an ex vivo burn model, coinciding with the translocation of its C-terminal region into the nucleus. We identified the cleavage site of GPRC5A by N-TAILS analysis, and cathepsin G was characterized as responsible for proteolysis in cultured cells. To gain a deeper understanding of GPRC5A's role in keratinocyte, we performed GPRC5A knockdown in N/TERT-1 cells using short-hairpin RNA. Our findings strongly suggest a close association between GPRC5A and adhesion regulation pathways, but also demonstrate that GPRC5AKD enhanced cell adhesion while reducing cell migration and differentiation. Importantly, these effects were reversed by adding a recombinant polypeptide mimicking the C-terminal region of GPRC5A. Overall, our study reveals an unexpected role of GPRC5A in regulating keratinocyte behavior, implicating its C-terminal region translocation into the nucleus. These results open up interesting strategic pathways for wound healing.
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Project description:Increasing the understanding of the impact of changes in oncogenes and tumor suppressor genes is essential for improving the management of lung cancer. Recently, we identified a new mouse lung-specific tumor suppressor - the G-protein coupled receptor 5A (Gprc5a). We sought to understand the molecular consequences of Gprc5a loss and towards this we performed microarray analysis of the transcriptomes of lung epithelial cells cultured from normal tracheas of Gprc5a knockout and wild-type mice to define a loss-of-Gprc5a gene signature. Moreover, we analyzed differential gene expression patterns between Gprc5a knockout normal lung epithelial cells as well as lung adenocarcinoma cells isolated and cultured from tumors of NNK-exposed Gprc5a knockout mice.
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Project description:Prostate cancer is a high frequent disease. Early stage prostate cancer can be cured with high probability by early treatment, but hormone refractory prostate cancer and progressive prostate cancer is poor prognosis. Orphan GPCRs have the potential to become a drug discovery target in various carcinomas, but there are few reports in prostate cancer and there are still many possibilities. By big data analysis, we focused on the biological properties of the prostate cancer cell line and found GPRC5A from Orphan GPCR as one of the regulators of prostate cancer development. GPRC5A knock out by genomic editing in PC3, proliferative ability and bone metastasis was markedly suppressed. In prostate cancer cells, GPRC5A inhibit phosphorylation of CREB and affected the expression of cell cycle related genes. GPRC5A is also involved in the establishment of bone metastases, and correlated with prostate cancer metastasis and prognosis. These dates suggest that GPRC5A facilitates cell proliferation and progression of prostate cancer and can be a target for new prognostic marker or drug discovery of prostate cancer.
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